Ophthalmic treatment device, system, and method of use

ABSTRACT

Ophthalmic treatment systems and methods of using the systems are disclosed. The ophthalmic treatment systems include (a) a light source device; (b) at least one optical treatment head operatively coupled to the light source device, comprising a light source array, and providing at least one treatment light; and (c) a light control device, which (i) provides patterned or discontinuous treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye); or (ii) adjusts intensity of part or all of the light source array, providing adjusted intensity treatment light projection onto an eye (e.g., the cornea and/or sclera of an eye). The at least one treatment light promotes corneal and/or scleral collagen cross-linking.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of co-pending U.S. patent applicationSer. No. 15/271,668 filed on Sep. 21, 2016, which is a continuation ofU.S. patent application Ser. No. 14/206,847 filed on Mar. 12, 2014, nowU.S. Pat. No. 9,622,911, which claims the benefit of U.S. ProvisionalPatent Application No. 61/785,336 filed on Mar. 14, 2013 and is acontinuation in part of U.S. patent application Ser. No. 13/034,488filed on Feb. 24, 2011 which claims the benefit of U.S. ProvisionalPatent Application No. 61/388,362 filed on Sep. 30, 2010.

BACKGROUND

Corneas and scleras derive their structural strength, shape andintegrity from collagen. The strength of the intertwined collagenstrands is a function of covalent cross-links established between andwithin collagen strands and between collagen and glycoproteins in thematrix. In structurally robust corneas and scleras, an enzyme calledlysyl oxidase performs the collagen cross-linking function in a processcalled oxidative deamination using molecular oxygen present in thetissue. The biomechanical strength of corneal and scleral collagen canbe reduced by a number of conditions including iatrogenic effect fromsurgical intervention, prosthesis, or medications, or the cause ofcorneal or scleral weakness can be congenital, idiopathic or due tomicrobial causes or trauma. In these cases of corneal or scleralweakness, interventional strategies to strengthen the collagen or toreduce infections are often employed.

SUMMARY OF THE DISCLOSURE

Disclosed herein, in certain embodiments, are ophthalmic treatmentsystems, comprising (a) a light source device; (b) at least one opticaltreatment head operatively coupled to the light source device,comprising a light source array, and providing at least one treatmentlight; and (c) a light control device, which (i) provides patterned ordiscontinuous treatment light projection onto an eye (e.g., the corneaand/or sclera of an eye); and/or (ii) adjusts intensity of part or allof the light source array, providing adjusted intensity treatment lightprojection onto an eye (e.g., the cornea and/or sclera of an eye). Insome embodiments, the light control device directs the at least onetreatment light. In some embodiments, the light source array devicecomprises a light source or a plurality of light sources. In someembodiments, the system further comprises an optical projection deviceconfigured to direct the at least one treatment light onto an eye (e.g.,the cornea and/or sclera of an eye). In some embodiments, the systemfurther comprises an optical projection device configured to direct theat least one treatment light onto a portion of an eye (e.g., the corneaand/or sclera of an eye). In some embodiments, the light control deviceapplies the at least one treatment light to an eye (e.g., the corneaand/or sclera of an eye) in a predetermined pattern. In someembodiments, the light control device applies the at least one treatmentlight to an eye (e.g., the cornea and/or sclera of an eye) in aplurality of predetermined patterns. In some embodiments, the lightcontrol device independently blocks or unblocks part of the light sourcearray and independently adjusts the intensity of part of the lightsource array such that the array provides a plurality of treatmentlights having a plurality of intensities. In some embodiments, the lightsource comprises one or more laser diodes or LEDs. In some embodiments,a controller controls the light source to provide discontinuoustreatment light projection onto the eye at a predetermined treatmentlight exposure period between 1 second and 10 minutes. In someembodiments, each treatment light exposure period of the discontinuoustreatment is between around 5 seconds and 25 seconds. In someembodiments, the treatment light exposure period is around 15 seconds.In some embodiments, the treatment light is in a frequency range from350 to 400 nm. In some embodiments, the at least one treatment lightpromotes collagen cross-linking. In some embodiments, the at least onetreatment light promotes corneal or scleral collagen cross-linking. Insome embodiments, corneal or scleral collagen cross-linking strengthensthe cornea and/or sclera, or reduces or treats infections in the eye. Insome embodiments, the light control device comprises a light modulatingdevice which partially or entirely blocks or unblocks the part or all ofthe light source array, providing the discontinuous treatment lightprojection on the eye (e.g., the cornea and/or sclera of an eye). Insome embodiments, the light modulating device is a shutter or filter. Insome embodiments, the light modulating device is manually operated. Insome embodiments, the light modulating device is operatively connectedto a controller which controls movement of the light modulating device.In some embodiments, the controller comprises a microprocessor forcontrolling the blocking or unblocking of the part or all of the lightsource array. In some embodiments, the controller comprises an input foroperator selection of parameters and duration for the discontinuouslight projection on the cornea and/or sclera. In some embodiments, thelight control device comprises an intensity control device which adjustsintensity of part or all of the light source array, providing theadjusted intensity treatment light projection onto an eye (e.g., thecornea and/or sclera of an eye). In some embodiments, the intensitycontrol device is manually operated. In some embodiments, the intensitycontrol device comprises a microprocessor to adjust intensity of part orall of the light source array. In some embodiments, the intensitycontrol device comprises an input for operator adjustment of lightintensity. In some embodiments, the system further comprises a patterncontrol device which provides patterned treatment light projection ontoan eye (e.g., the cornea and/or sclera of an eye). In some embodiments,the pattern control unit is part of a light mask. In some embodiments,the pattern control unit comprises at least one filter or shutter. Insome embodiments, the pattern control unit comprises a microprocessorwhich controls movement of the pattern control unit. In someembodiments, the pattern control device comprises an input for operatorcontrol of the patterned treatment light projection. In someembodiments, the pattern control unit moves. In some embodiments, thepattern control unit rotates. In some embodiments, the system furthercomprises a control unit which adjusts movement of the pattern controldevice. In some embodiments, the system further comprises a sensordevice. In some embodiments, the blocking and unblocking of part or allof the light source array, or the adjusting of the intensity of part orall of the light source array, is controlled or adjusted according todata collected from the sensor device. In some embodiments, the sensordevice is an optical collection device. In some embodiments, the opticalcollection device collects photoluminescent emissions from an eye (e.g.,the cornea and/or sclera of an eye). In some embodiments, the sensordevice comprises a photoluminescent monitoring module which measures theintensity of photoluminescent emissions from an eye (e.g., the corneaand/or sclera of an eye). In some embodiments, the photoluminescentmonitoring module comprises a first band pass filter connected to theoutput of the optical collection device, the first band pass filterhaving a center wavelength corresponding to the peak of fluorescenceemission of the photosensitizer, and a first sensor which receives theoutput of the first band pass filter output to produce a first outputsignal dependent on the detected fluorescence emission from the eye(e.g., the cornea and/or sclera of an eye). In some embodiments, thephotoluminescent monitoring module further comprises a second band passfilter connected to the output of the optical collection device inparallel with the first band pass filter, the second band pass filterhaving a center wavelength corresponding to the peak of phosphorescenceof an excited state of the photosensitizer, a second sensor whichreceives the output of the second band pass filter to produce a secondoutput signal dependent on the intensity of detected phosphorescencefrom the eye (e.g., the cornea and/or sclera of an eye). In someembodiments, the system further comprises a processor which receivesfirst and second output signals and which is configured to process thefirst output signal and produce an output signal which varies inresponse to variations in a concentration of the photosensitizer in aneye. In some embodiments, the sensor device comprises an environmentalmonitoring module which monitors concentrations of photosensitizer,oxygen, or both in the eye. In some embodiments, the system furthercomprises a fixation light upon which an eye is focused, providing astatic treatment area. In some embodiments, the system further comprisesa periodical visual or audio cue. In some embodiments, the systemfurther comprises an auxiliary light source configured to be turned onif the at least one treatment light is discontinued or adjusted. In someembodiments, the optical treatment head is positioned at a workingdistance from the eye sufficient to allow access to the eye (e.g., thecornea and/or sclera of an eye). In some embodiments, the workingdistance is at least two inches. In some embodiments, the workingdistance is about three inches. In some embodiments, the workingdistance is from about three inches to about six inches. In someembodiments, the light source device comprises at least onesingle-wavelength light source. In some embodiments, the light sourcedevice comprises a plurality of single-wavelength light sources. In someembodiments, the at least one single-wavelength light source is an LEDor a laser diode. In some embodiments, the light source device comprisesa multi-wavelength light source. In some embodiments, the light sourcedevice further comprises a wavelength control device operatively coupledto the multi-wavelength light source. In some embodiments, thewavelength control device allows transmission of treatment light of atleast one predetermined wavelength band and blocks transmission of lightoutside of the predetermined wavelength band. In some embodiments, themulti-wavelength light source comprises a short-arc lamp. In someembodiments, the short-arc lamp is a mercury lamp, a mercury halidelamp, or a xenon lamp. In some embodiments, the multi-wavelength lightsource further comprises a beam isolator configured to direct treatmentlight of wavelength ranging from about 330 to about 380 nm to thewavelength control device. In some embodiments, the beam isolator isconfigured to direct both UVA and blue light to the wavelength controldevice. In some embodiments, beam isolator comprises a UVA and bluelight reflective dichroic mirror. In some embodiments, the wavelengthcontrol device allows selective transmission of treatment light of atleast two different predetermined wavelength bands. In some embodiments,the wavelength control device comprises at least first and secondfilters and a controller configured to alternate between the first andsecond filters. In some embodiments, the first filter is a UVA filterand the second filter is a blue light filter. In some embodiments, theUVA filter has about 10 nm bandwidth at 365 nm and the blue light filterhas about 10 nm bandwidth at 405 nm. In some embodiments, the systemfurther comprises a support stand, an adjustable mounting assembly on asupport stand, the optical treatment head supported on the mountingassembly, wherein the mounting assembly is configured for X and Ydirectional adjustment of the position of the optical treatment headrelative to the eye. In some embodiments, the adjustable mountingassembly comprises a goose neck mounting arm connected to the opticaltreatment head. In some embodiments, the mounting assembly comprises anarticulated arm having a first end mounted for vertical slidingadjustment on the support stand and a second end supporting the opticaltreatment head. In some embodiments, the mounting assembly includes aswivel joint configured for adjustment of an angle of the light beamdirected from the optical treatment head to the eye (e.g., the corneaand/or sclera of an eye). In some embodiments, the system comprises afirst and a second optical treatment head, each having a light sourcearray. In some embodiments, the first and the second optical treatmentheads each independently project treatment light onto the left eye(e.g., the cornea and/or sclera of the left eye) or the right eye (e.g.,the cornea and/or sclera of the right eye). In some embodiments, thesystem comprises a mounting assembly having a first portion and secondportion each independently associated with one of the two opticaltreatment heads. In some embodiments, the mounting assembly comprises anarticulated arm assembly having a first portion slidably associated withthe support stand, the first portion and second portions of the mountingassembly being pivotally connected to the first portion of thearticulation arm assembly. In some embodiments, one of the end portionsis articulated. In some embodiments, the mounting assembly furthercomprises first and second swivel joints between the first and secondoptical treatment heads, respectively. In some embodiments, the systemfurther comprises locking devices configured for releasable locking thefirst optical treatment head and the second optical treatment head, at aselected X, Y and Z adjusted position relative to a respective eye of apatient. In some embodiments, the system comprises a first and a secondoptical treatment head each including projection optics and configuredto project respective treatment light onto the right and left eyes(e.g., the cornea and/or sclera of the left and right eyes) at apredetermined working distance from the optical heads. In someembodiments, the first optical treatment head and second opticaltreatment head are adjustably mounted for at least x and y directionadjustment of the position of the optical treatment head relative to therespective eyes. In some embodiments, the system further comprises anintensity adjustment module configured to independently adjust intensityof part or all of the light source array projected by the first opticaltreatment head and second optical treatment head. In some embodiments,the system further comprises an adjustable mounting assembly configuredfor adjusting the separation between the first and second opticaltreatment heads and the distance of each optical treatment head from therespective eyes. In some embodiments, the adjustable mounting assemblyincludes independent swivel joints configured for adjusting an angle ofeach optical head relative to the respective eye. In some embodiments,the system further comprises an adjustment mechanism configured forvarying distance of the optical treatment head from the eye. In someembodiments, the light source device further comprises an aestheticlight which is visible to an observer, and optionally not visible to apatient. In some embodiments, the light source device further comprisesa plurality of aesthetic lights which are visible to an observer, andoptionally not visible to a patient. In some embodiments, the aestheticlights are activated when the light source device is activated andproviding the at least one treatment light.

Described herein, in certain embodiments, are methods of producing atreatment light for use in phototherapy treatment of an eye (e.g., thecornea and/or sclera of an eye), comprising (a) directing light from amulti-wavelength light source to a wavelength control device; (b)isolating and directing treatment light of at least one predeterminedwavelength band to at least one optical treatment head ; and (c)projecting a light beam from the optical treatment head and focusing thebeam to produce a light spot of predetermined size and shape on the eye(e.g., the cornea and/or sclera of the eye) at a predetermined workingdistance from the optical treatment head, whereby the optical treatmenthead is positioned at a distance from the eye sufficient to allow accessto the eye (e.g., the cornea and/or sclera of the eye). In someembodiments, the method comprises splitting the at least one treatmentlight along separate first and second optical paths, and directing theseparated treatment lights to a first optical treatment head and asecond optical treatment head for simultaneous treatment of right andleft eyes (e.g., the cornea and/or sclera of the right and left eyes).In some embodiments, the method further comprises adjusting a distancebetween the first optical treatment head and the second opticaltreatment head based on a distance between the right and left eyes. Insome embodiments, the method further comprises independently adjustingthe first optical treatment head and the second optical treatment headto adjust an angle at which the at least one treatment light isprojected on the respective eye (e.g., the cornea and/or sclera of theeye). In some embodiments, the method further comprises independentlyadjusting the intensity of the at least one treatment light applied tothe respective eye (e.g., the cornea and/or sclera of the eye). In someembodiments, the method further comprises blocking and unblocking the atleast one treatment light beam at predetermined time intervals toprovide discontinuous light projection on the cornea and/or sclera. Insome embodiments, the method further comprises contacting the eye (e.g.,the cornea and/or sclera of the eye) with a photosensitizer. In someembodiments, the photosensitizer is riboflavin, rose Bengal, otherphotosensitizers, or derivatives thereof In some embodiments, the methodfurther comprises monitoring the level of photoluminescent emissionsfrom the eye (e.g., the cornea and/or sclera of the eye) duringtreatment and determining approximate photosensitizer concentration inthe eye (e.g., the cornea and/or sclera of the eye) is based on thelevel of photoluminescent emissions. In some embodiments, the methodfurther comprises controlling an aperture in the optical treatment head,whereby intensity of the at least one treatment light and the size ofthe light spot is variable.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an embodiment of a bilateral treatmentsystem or photochemical treatment and monitoring system;

FIG. 2 is a block diagram illustrating the optical source unit of FIG.1;

FIG. 3 is a view of an embodiment of the front control panel of theillumination source unit of FIG. 2;

FIG. 4 is a top perspective view of the bilateral optical head of FIG.1;

FIG. 5 is a cross-sectional view of an embodiment of an opticaltreatment head;

FIG. 6 is a perspective view of the left hand optical treatment head andhousing with sensor attached, of FIG. 1;

FIG. 7 is a layout view of the intensity adjustment mechanism for theexcitation light guides;

FIG. 8A is a cross-sectional view through an eye with a normal corneaand/or sclera;

FIG. 8B is a cross-sectional view through an eye affected by keratoconusoffset from the central axis of the eye;

FIG. 9 is a side cross sectional view of the left hand optical deliveryand sensor head of FIG. 4;

FIG. 10 is a bottom view the left hand optical delivery and monitoringhead of FIG. 4;

FIG. 11 is a component layout view of one embodiment of a photoluminescent measuring module in the system of FIGS. 1 to 10 and 15, withthe inputs from the bifurcated light guides from each optical head andthe photodiodes and amplifiers for monitoring the fluorescence andphosphorescence from each eye;

FIG. 12 shows a top view of one embodiment of a dodging tool for use inevaluating lateral riboflavin dispersion in conjunction with fluorescentintensity monitoring;

FIG. 13 is a perspective view of one embodiment of a corneal and/orscleral treatment head with sensor device and manually operatedmechanical light modulating device (for example, a shutter and/orfilter);

FIG. 14 is a perspective view of one embodiment of a corneal and/orscleral treatment head with sensor device and microprocessor-controlledmechanical light modulating device (for example, a shutter and/orfilter) attached;

FIG. 15 is a perspective view of one embodiment of a corneal and/orscleral treatment head with sensor device attached, andmicroprocessor-controlled dimmer switch attached to the light source andsensor device;

FIG. 16 is a perspective view of one embodiment of a corneal and/orscleral treatment head with sensor device and manually operated filtersystems attached;

FIG. 17 is a perspective view of one embodiment of a corneal and/orscleral treatment head with sensor device and automatically operatedfilter system attached to microprocessor and sensor device;

FIG. 18 is a perspective view of one embodiment of a rotating radiationpattern assembly which is attached to the corneal and/or scleraltreatment head casing;

FIG. 19 is a perspective view of one embodiment of a filter with anaperture which allows for unequal doses of UVA/blue light to be appliedto various portions of the treatment area;

FIG. 20 illustrates one embodiment of a kit of optical masks or reticleswith treatment light transmitting openings of various differentpatterns, shapes, and sizes;

FIG. 21 is a perspective view of one embodiment of an additional lightsource utilized to reduce the startling effect by mitigating dramaticchanges in light intensity or color seen by the patient;

FIG. 22 is a perspective view of one embodiment of a fixation light;

FIG. 23 is a front perspective view of another embodiment of anophthalmic treatment system or device for corneal and/or scleraltreatment;

FIG. 24 is a rear perspective view of the ophthalmic treatment system ofFIG. 23;

FIG. 25 is a perspective view of the control system housing and touchscreen user interface of FIGS. 23 and 24, with the front wall of thecontrol system housing broken away to reveal internal parts of thesystem;

FIG. 26 is bottom plan view of one of the treatment heads of FIGS. 23and 24;

FIG. 27 is a view similar to FIG. 26 with the lower wall of thetreatment head housing removed to reveal the internal system components;

FIG. 28 is a cross-sectional view on the lines 28-28 of FIG. 27;

FIG. 29 is a front plan view of the reticle wheel of FIG. 28; and

FIG. 30 is a block diagram of the system of FIGS. 23 to 29.

It should be understood that the drawings are not necessarily to scaleand that the disclosed embodiments are sometimes illustrateddiagrammatically and in partial views. In certain instances, detailswhich are not necessary for an understanding of the disclosed apparatusor method which render other details difficult to perceive are omitted.It should be understood, of course, that this disclosure is not limitedto the particular embodiments illustrated herein.

DETAILED DESCRIPTIONS

The present disclosure relates generally to ophthalmic device, system,and method for treating a cornea or sclera of an eye, in particular fortreating a cornea or sclera weakened by various medical or surgicalconditions, for reducing infection, or for imparting refractive changesto the entire or selected portions of the eye (e.g., the cornea orsclera) to correct or otherwise improve vision.

Corneal and/or scleral collagen cross-linking shortens the length andincreases the diameter of corneal and/or scleral collagen. In somecases, corneal and/or scleral collagen cross-linking is beneficial incorneas and/or scleras that would benefit from refractive correction toimprove vision. Corneal and/or scleral tissue segments can becross-linked selectively so as to control and customize refractivechanges to meet the individual vision correction needs of the patient.

One method of cross-linking corneal and/or scleral collagen orstrengthening collagen to impart refractive change and improve vision isphotochemical cross-linking. The method of photochemical cross-linkinguses a photosensitizer, usually riboflavin monophosphate, and UVA lightto promote the cross-linking of the collagen fibrils. Photochemicalcross-linking of the cornea has been demonstrated to slow, stop, orreverse the progression of compromised collagen in patients withkeratoconus and ectasia.

Disclosed herein, in certain embodiments, are ophthalmic treatmentsystems, comprising a light source device or light source array and alight control device, which blocks or unblocks the part or all of thelight source array for predetermined intervals, and which may beconfigured to provide patterned or discontinuous treatment lightprojection onto an eye (e.g., the cornea and/or sclera of an eye); orwhich may adjust intensity of part or all of the light source array,providing adjusted intensity treatment light projection onto an eye(e.g., the cornea and/or sclera of an eye). In some embodiments, thelight source may comprise a plurality of light sources.

As used herein, “light source array” means an ordered or disorderedarrangement of at least one light source. In some embodiments, the lightsource array comprises one light source. In some embodiments, the lightsource array comprises a plurality of light sources. In someembodiments, the plurality of light sources are in an orderedarrangement. In some embodiments, the plurality of light sources are ina disordered arrangement.

Discontinuous/Adjustable/Patterned Light Projection

In some embodiments of the ophthalmic treatment systems disclosedherein, the light control device includes a manual ormicroprocessor-controlled mechanical light modulation device (e.g., ashutter or filter) which is placed in the path of the light beam, at theappropriate position, providing discontinuous projection of treatmentlight on the eye (e.g., the cornea and/or sclera). In some embodiments,the on/off times for the discontinuous projection of treatment light onthe eye (e.g., the cornea and/or sclera) is dependent on theconcentrations of the photosensitizer (both excited state and groundstate) and/or the partial pressure of the oxygen in the eye (e.g., thecornea and/or sclera). In some embodiments, the on/off times for thediscontinuous projection of treatment light on the eye (e.g., the corneaand/or sclera) is controlled manually. In another embodiment, the on/offtimes for the discontinuous projection of treatment light on the eye(e.g., the cornea and/or sclera) is controlled automatically based oninput by the physician at a control unit to determine overall treatmenttime and duration of on/off cycles. In another embodiment, the on/offtimes for the discontinuous projection of treatment light on the eye(e.g., the cornea and/or sclera) is microprocessor-controlled on thebasis of the ratio of riboflavin phosphorescence at 605 nm in relationto riboflavin fluorescence at 525 nm detected from a measurement/sensordevice in each treatment head. As the ratio of triplet state riboflavinphosphorescence of 605 nm/525 nm fluorescence drops, the microprocessorcontrols on/off times in accordance with the riboflavin concentrationand/or oxygen partial pressure. When the light is shuttered or filtered,the oxygen consumption by the riboflavin triplets stops and the eye(e.g., the cornea and/or sclera) reoxygenates from the tear film or fromoxygenated ophthalmic solutions applied to the eye (e.g., the corneaand/or sclera). In another embodiment, thediscontinuous/adjustable/patterned light projection device is providedseparately for use in other commercially available UVA/blue lightemitting devices.

In some embodiments of the ophthalmic treatment systems, the lightcontrol device includes a manual or microprocessor-controlled opticalshutter (e.g. a UVA/blue light filter) which is placed in the path ofthe light beam, at the appropriate position, so as to providediscontinuous projection of treatment light on the eye (e.g., the corneaand/or sclera). In some embodiments, the filtered/unfiltered times forthe discontinuous projection of treatment light on the eye (e.g., thecornea and/or sclera) is dependent on the concentrations of thephotosensitizer (both excited state and ground state) and/or the partialpressure of the oxygen in the eye (e.g., the cornea and/or sclera). Insome embodiments, the filtered/unfiltered times for the discontinuousprojection of treatment light on the eye (e.g., the cornea and/orsclera) is controlled manually. In another embodiment, thefiltered/unfiltered times for the discontinuous projection of treatmentlight on the eye (e.g., the cornea and/or sclera) is automatically basedon input by the physician at a control unit to determine overalltreatment time and duration of filtered/unfiltered cycles. In anotherembodiment, the filtered/unfiltered times for the discontinuousprojection of treatment light on the eye (e.g., the cornea and/orsclera) are microprocessor-controlled on the basis of the ratio ofriboflavin phosphorescence at 605 nm in relation to riboflavinfluorescence at 525 nm detected from a measurement/sensor device in eachtreatment head. As the ratio of triplet state riboflavin phosphorescenceof 605 nm/525 nm fluorescence drops, the microprocessor controlsfiltered/unfiltered times in accordance with the riboflavinconcentration and/or oxygen partial pressure. When the light isfiltered, the oxygen consumption by the riboflavin triplets stops andthe cornea and/or sclera reoxygenates from the tear film or fromoxygenated ophthalmic solutions applied to the eye (e.g., the corneaand/or sclera).

In some embodiments of the ophthalmic treatment systems, the lightcontrol device includes a manual or microprocessor-controlled intensitycontrol device (e.g. a dimming mechanism or switch) so as to provide forgradual decreases and increases in the UVA light intensity. Withoutwishing to be bound by any particular theory, it is contemplated thatthe gradual intensity adjustment mitigates one or more of startlingeffect, fixation loss, de-centered treatment, and Bells phenomenon. Insome embodiments, the dimming mechanism is configured to provide periodsof decreased UVA light, such that tissue reoxygenation occurs, andperiods of increased UVA light, such that cross linking occurs. In someembodiments, the dim/bright times for the adjustable projection oftreatment light on the eye (e.g., the cornea and/or sclera) is dependenton the concentrations of the photosensitizer (both excited state andground state) and/or the partial pressure of the oxygen in the eye(e.g., the cornea and/or sclera). In some embodiments, the dim/brighttimes for the discontinuous projection of treatment light on the eye(e.g., the cornea and/or sclera) is controlled manually. In anotherembodiment, the dim/bright times for the discontinuous projection oftreatment light on the eye (e.g., the cornea and/or sclera) isautomatically based on input by the physician at a control unit todetermine overall treatment time and duration of dim/bright cycles. Inanother embodiment, the dim/bright times for the discontinuousprojection of treatment light on the eye (e.g., the cornea and/orsclera) are microprocessor-controlled on the basis of the ratio ofriboflavin phosphorescence at 605 nm in relation to riboflavinfluorescence at 525 nm detected from a measurement/sensor device in eachtreatment head. As the ratio of triplet state riboflavin phosphorescenceof 605 nm/525 nm fluorescence drops, the microprocessor controlsdim/bright times in accordance with the riboflavin concentration and/oroxygen partial pressure. When the light is filtered, the oxygenconsumption by the riboflavin triplets stops and the eye (e.g., thecornea and/or sclera) reoxygenates from the tear film or from oxygenatedophthalmic solutions applied to the eye (e.g., the cornea and/orsclera).

In some embodiments of the ophthalmic treatment systems, the lightcontrol device includes a manual or microprocessor-controlled patterncontrol device, such as a light mask or a reticle, to provide patternedprojection of the at least one treatment light onto the eye (e.g., thecornea and/or sclera). In some embodiments, the pattern control deviceis configured to simultaneously transmit part of the at least onetreatment light such that cross linking occurs, and block the rest ofthe at least one treatment light such that tissue reoxygenation occurs.In some embodiments, masks or reticles of different patterns may beselectively positioned in the treatment light path to the eye and may becontrolled to provide for variable durations of illumination andnon-illumination, resulting in varying levels and depths of cornealand/or scleral strengthening in selected areas to impart varying levelsof corneal and/or scleral refractive change. In some embodiments, thepattern control device is one or more reticles having apertures thatallow a variety of different light distribution patterns and sizes to beselected by the physician. The patterns and sizes allow the physician todirect light emission to pre-selected sections or portions of the eye(e.g., the cornea and/or sclera) that benefit from corneal and/orscleral strengthening, either to strengthen weakened corneal and/orscleral tissue, or to impart selective strengthening and resultingrefractive changes to improve visual acuity. In some embodiments, thepatterns and durations of the patterned light projection are dependenton the concentrations of the photosensitizer (both excited state andground state) and/or the partial pressure of the oxygen in the eye(e.g., the cornea and/or sclera).

One technical feature of the present disclosure is that thediscontinuous/adjustable/patterned treatment light projection allowsreoxygenation during treatment. It is found that oxygen is consumedduring cross-linking and needs to be replenished, such as through theanterior corneal and/or scleral surface. When excitation energy isapplied to the surface of the eye (e.g., the cornea and/or sclera), theoxygen that is reentering the eye (e.g., the cornea and/or sclera) isconsumed at a rate that exceeds the reoxygenation diffusion rate and theeye (e.g., the cornea and/or sclera) remains hypoxic, particularly inthe posterior portions, under continuous wave conditions. It is notedthat blue light excitation gives the user an option for increasedreoxygenation of the posterior stroma. Blue light is less absorbed inthe anterior cornea and/or sclera and accordingly the oxygen consumptionrate is lowered. This allows more of the replenishment oxygen to reachthe posterior stromal region.

For example, the triplet riboflavin molecules created duringphotochemical therapy either form singlet oxygen created in a Type IIreaction or hydrogen peroxide by a Type I reaction. In the presence ofphysiological amounts of oxygen of 20 mm Hg partial pressure the Type IIsinglet oxygen reaction predominates. Under conditions of subnormaloxygen availability (less than 5 mm Hg of O2), the Type I hydrogenperoxide reaction predominates. It is contemplated that the stromalregion is hypoxic under the current protocol of continuous 3.0 mw/cm2UVA and 0.1% riboflavin cornea. The available oxygen content of thestroma is consumed almost immediately as demonstrated by the followingcalculation. Given the volume occupied by a 500-micron thick cornea andthe reported literature value of 35 micromolar oxygen in the stroma, thetotal amount of oxygen in the cornea is about 1.4×10-9 moles. Thequantum yield of singlet oxygen from riboflavin irradiation is 0.52,indicating that approximately 2 photons of absorbed energy consume 1unit of molecular oxygen. Accordingly, only 2.8×10-9 moles of photonsare required to consume all of the available stromal oxygen. Using therelationship E=hv the amount of energy to deplete all of the corneaoxygen is less than 1 mJ of UVA light. It is contemplated that oxygen isconsumed rapidly (e.g. in seconds) after the treatment starts. Thus, thereoxygenation provided by the disclosed treatment system, such asthrough discontinuous/adjustable/patterned treatment light projection,allows improved cross-linking.

Photosensitizer/Oxygen Monitor

In some embodiments, the ophthalmic treatment systems includes a devicefor monitoring the concentration of the photosensitizer (e.g.riboflavin, rose Bengal, other photosensitizers, or derivatives thereof)in the eye (e.g., the cornea and/or sclera) so the physician maydiscontinue, adjust, or selectively apply the at least one treatmentlight to achieve the optimal depth of penetration while still reducingthe risk of damage to the endothelial cells. In addition, thephotosensitizer monitor also allows the physician to determine whensufficient riboflavin is present in the eye (e.g., the cornea and/orsclera) during light treatment. In some embodiments, an opticalcollection device is mounted adjacent to the optical head and isconfigured to collect photoluminescent emissions from the eye (e.g., thecornea and/or sclera) during treatment. The output of the opticalcollection device is connected to a photoluminescence monitoring unit.

Without wishing to be bound by any particular theory, it is contemplatedthat knowledge of the amount of photoluminescence allows the physicianto adjust the treatment to reduce the potential loss of endothelialcells by excess UV radiation, which is attributable to low concentrationof the riboflavin, excessive treatment light intensity, toxic peroxidesor reactive oxygen species (ROS) generated under hypoxic conditions, orcombinations thereof. In addition, without wishing to be bound by anyparticular theory, it is contemplated that excessive riboflavin in theeye (e.g., the cornea and/or sclera) not only prevents significantamounts of UV from reaching the endothelial cells in a sunscreen-likeeffect, but also limits the cross-linking depth to the anterior portionof the stroma. Measurement of riboflavin concentration allows thephysician to monitor for excessive riboflavin during the procedure andto take appropriate steps to mitigate such conditions.

In some embodiments, the photosensitizer monitor is based upon thedetection of the photoluminescence of the photosensitizer as itinteracts with the excitation light. As used in the present disclosure,“photoluminescence” is defined as the combined radiation given off bythe fluorescence of photosensitizer and the radiation given off asphosphorescence from the excited state of the photosensitizer (e.g.triplet state of riboflavin). The emission intensity of thephotoluminescent radiation is a function of the light wavelength, thelight intensity and the concentration of the riboflavin. Since thewavelength and intensity of the applied light is known, the emissionintensity of photoluminescent radiation from the patient's eye (asdetermined by the photoluminescence monitoring unit and a suitablemicroprocessor receiving the output of the monitoring unit) is used tomeasure the riboflavin concentration. In some embodiments, thephotosensitizer monitor uses colorimetry (e.g. color comparison charts)to determine the concentration of the photosensitizer.

In some embodiments, the photosensitizer concentrations measured areprovided to the physician on a display unit associated with the systemto allow the physician to adjust the treatment light intensity orwavelength, switch to discontinuous light projection, or take othersteps in response to detected reduction or increase in concentration ofriboflavin.

In some embodiments, the ophthalmic treatment systems further comprisesa device for monitoring molecular oxygen or oxygen partial pressure inthe eye (e.g., the cornea and/or sclera). In some embodiments, theoxygen monitor is based on the triplet state riboflavin phosphorescenceat 605 nm in relation to riboflavin fluorescence at 525 nm. As the ratioof triplet state of riboflavin phosphorescence of 605 nm/525 nmfluorescence decreases, the quantum yield of the triplet state moleculesdecreases, thereby indicating a decrease in the partial pressure ofoxygen in the eye (e.g., the cornea and/or sclera).

Without wishing to be bound by any particular theory, it is contemplatedthat, during the course of the irradiation, the riboflavinphoto-oxidizes and degrades to a form that does not fluoresce or createtriplet molecules. Under ideal conditions, the phosphorescence woulddegrade at the same rate. However, the presence of oxygen is requiredfor phosphorescence of riboflavin to occur in solutions, and oxygen alsoquenches the phosphorescence of the riboflavin. The quenching of thephosphorescence by oxygen corresponds to the reduction in thephosphorescence signal. Since some degradation in the tripletphosphorescence signal is expected as a result of riboflavindegradation, the optimal index for monitoring the oxygen quenching oftriplet riboflavin is the ratio of the phosphorescence to thefluorescence. The phosphorescence signal is compared to the fluorescencesignal during calibration and expressed as a ratio (e.g. 30:100). As thereaction proceeds over time, the ratio decreases as the phosphorescencesignal decreases, indicating quenching of triplet riboflavin bymolecular oxygen. In some embodiments, the decrease in the ratio is usedas a proxy measure of the singlet oxygen production. As the ratio of thephosphorescent/fluorescent signal decreases, the efficiency of singletoxygen production decreases, allowing the ratio to level off at somepoint, which signals to the operator the need to reoxygenate the eye(e.g., the cornea and/or sclera) by discontinuous/adjustable/patternedlight projection.

Projection Distance

In some embodiments, the projection optics are configured to provide adistance of the patient's eye from the optical head of approximately twoinches or greater. Other working distances, such as about three inchesor from about three inches to about six inches, are provided inalternative embodiments. The increased working distance between theoptical head and patient's eye provides improved physician visualizationand better access to the eye during treatment, for example to add morephotosensitizer drops or other ophthalmic solutions, or for othertreatment aids.

Fixation Light

In some embodiments, the ophthalmic treatment systems further comprisesa fixation light either attached to or separated from the treatmentdevice. During periods of continuous ordiscontinuous/adjustable/patterned light projection, the patient's eyesnaturally deviate from the desired position. Fixing the patient's lineof sight, such as on a fixation light, allows the patient's eyes toremain correctly aligned and/or focused. In some embodiments, thefixation light is independently movable in relation to the opticaltreatment head(s) to fix the patient's eyes at certain directions and/orangles, thereby allowing the physician to deliver light in a beampath/direction that is independent of the patient's visual axis. In someembodiments, the fixation light is positioned within the line of sightof both eyes of the patient, at a distance from each eye that issufficient to prevent double vision of the fixation light. In someembodiments, the fixation light emits red light, or other light withinthe visible spectrum such as green light, which is easily viewable by apatient during treatment. In another embodiment the fixation lightperiodically blinks or emits an audio cue to reacquire and/or maintainthe patient's attention.

Auxiliary Light Source

In some embodiments, the ophthalmic treatment systems comprises anotherlight source in addition to the UVA/blue treatment light which is turnedon/off coincident with the at least one treatment light entering aperiod of discontinued/filtered/dimmed or entering a period ofcontinued/unfiltered/non-dimmed light. In some embodiments, theadditional light emission is integral to the UVA/blue treatment lightpath and at least partially compensates for the changes in color andlight intensity seen by patients during periods of varying UVA/blueillumination, reducing the startle effect when the UVA or blue treatmentbean is turned on and off In some embodiments, the separate light sourcehas a wavelength in the visible light spectrum that is not highlyabsorbed by riboflavin and therefore does not result in oxygenconsumption from riboflavin triplet formation, yet appears to thepatient to be of the same or similar color as that of excitedriboflavin. In some embodiments, the auxiliary or anti-startle lightsource may be a green light LED. Without wishing to be bound by anyparticular theory, it is contemplated that the gradual intensityadjustment mitigates one or more of startling effect, fixation loss,de-centered treatment, and Bells phenomenon.

Light Source

In some embodiments, the treatment device comprises a multi-wavelengthlight source. In some embodiments, the multi-wavelength light source isa full-spectrum light source that is filtered to give a narrow band ofexcitation energy within the UVA/blue light spectrum, and iscontrollable to provide output light in at least two differentwavelengths. In some embodiments, the light source is a short-arc lampsuch as a mercury or mercury halide lamp or a short-arc xenon lamp,which emits UVA light as well as light in other wavelengths. In someembodiments, the light source unit further comprises an optical systemwhich isolates light to a light beam in the wavelength required fortreating the patient and provides the isolated light beam to the lightguide for transmission to the optical treatment head. In someembodiments, the optical system comprises a focusing device for focusingradiation from the lamp along an optical path and a beam isolatingassembly in the optical path which is configured to direct light in aselected wavelength range into the first end of the light guide. In someembodiments, the beam isolating assembly comprises a reflective dichroicmirror which reflects light in the UVA/blue range of around 340 nm to470 nm and passes other radiation emitted by the lamp, and a filter inthe path of reflected light from the mirror which directs light of apredetermined wavelength or wavelength band to the wavelength controldevice.

In some embodiments, the light source is one single or limitedwavelength light source or multiple single wavelength light source, andmay be one or more light emitting diodes (LED) or laser diodes andprovides isolated light beams at selected wavelengths or limitedwavelength ranges.

Wavelength Control Device

In some embodiments, a wavelength control device selectively provideslight at one or multiple wavelength bands for treatment purposes (e.g.light in a UVA band and/or light in a blue or blue-violet band). In someembodiments, two different filters are provided which are selectivelypositioned in the light path, allowing selection of excitation energy inthe UVA band at 365 nm, or a narrow band of blue-violet radiation at 405nm. The option of UVA or blue radiation allows the surgeon flexibilityin achieving different depths of penetration into the cornea and/orsclera for the excitation light. For example, the molar extinctioncoefficient of riboflavin at 365 nm is about 10,000 and at 405 nm, theextinction coefficient is about 8000. If the riboflavin in the corneaand/or sclera is 0.003 molar, the 365 nm radiation deposits about 75% ofits energy to the riboflavin in the first 200 microns of the tissue,whereas with the 405 radiation only about 68% of the beam is absorbed inthe first 200 microns. The blue light delivers more energy in the deepertissue for deeper cross-linking. For patients with thin corneas and/orsclera, the UVA is used in some embodiments since the energy is absorbedmore quickly and less energy reaches the endothelium. For patients withthicker corneas and/or scleras, blue light is used in some embodimentsto penetrate deeper into the cornea and/or sclera. In a conventionalprocedure that uses 365 nm radiation, deepithelialization and 0.1%riboflavin soaking, cross-linking occurs to a depth of about 200microns, while damage (apoptosis) occurs deeper, at about 300 microns.The multi-wavelength excitation option of the disclosed system allowsfor deeper cross-linking (e.g. by blue light) if the surgeon determinesdeeper cross-linking is beneficial or necessary. This technical featureis heretofore unknown as currently marketed systems use monochromaticLEDs and do not allow for selectable excitation wavelengths.

One technical feature of the present disclosure heretofore unknown isthe option to select one of multiple wavelengths of the excitationlight. Without wishing to be bound by any particular theory, it iscontemplated that the wavelength determines the depth of penetration ofthe light into the riboflavin soaked cornea and/or sclera, which in turnaffects how much cross-linking is done at different depths of thecorneal stroma or sclera. The molar extinction coefficient of riboflavinis 10,066 cm−1/M at 365 nm but the molar extinction coefficient ofriboflavin is only 7884 cm−1/M at 405 nm. Under the Beer Lambert law,for a given wavelength and excitation energy, the fluorescent intensityof the photosensitizer (e.g. riboflavin) is linearly proportional to theconcentration of the fluorophore. Calculation of the light absorption byriboflavin at various depths of the cornea and/or sclera of the twowavelengths is possible using the Beer Lambert equation. In thisequation A=2−log10% T, where A is the absorbance of energy by a chemicalfluorophore and T is the transmission. The Beer Lambert law states thatA=Ebc where E is the molar extinction coefficient for a particularchemical and b is the path length of the measurement and c is theconcentration of the chemical. For a 0.1% solution of riboflavin at adepth of 500 microns the absorption value at 365 nm is calculated asA=1.10. The value of A for the same solution and path length for 405 nmradiation is calculated as A=0.86. From the formula A =2 - log10%T it isshown that 64% of the incident energy of 365 nm radiation is absorbed byriboflavin in the first 200 microns of the cornea and/or sclera. Thesame calculations at 405 nm indicate only 55% of the radiation isabsorbed by the riboflavin in the first 200 microns of the stroma orsclera. If the user determines that it is desirable to cross link deeperinto a cornea and/or sclera, the user has the option to select a morepenetrating radiation like 405 nm. If shallow cross-linking is moredesirable, the user has the option to select a less penetratingwavelength, such as 365 nm.

An additional feature of the 405 nm wavelength is the option to use lessintense light to accomplish the same amount of cross-linking. Theproduction of singlet oxygen by excited riboflavin triplet molecules isrelated to the number of incident photons, not the energy of thephotons. Riboflavin is excited at both 365 nm and 405 nm to its higherenergy states. By the formulation E=hv it is determined that a 405 nmphoton is 10% less energetic than a 365 nm photon, and that to haveequivalent stoichiometric reactions at 405 nm and 365 nm the incidentUVA light fluence is reduced to 90% of the blue light fluence.

Another additional feature of the blue light option for excitationenergy is that the lower absorption of blue light by riboflavin in theanterior cornea and/or sclera translates into less oxygen consumption inthe anterior stroma or sclera, and thereby allowing better reoxygenationof the posterior stroma or sclera, as discussed in more detail below.

Optical Coupling

In some embodiments, two components in the ophthalmic treatment systemsare optically coupled together through transmission of light from one toanother. In some embodiments, at least some of the components in theophthalmic treatment systems are optically coupled together through atleast one UV transmissive liquid light guide to produce homogeneouslight distribution. In some embodiments, the light source is coupled tothe wavelength control device through the liquid light guide. In someembodiments, the wavelength control device is coupled to the opticaltreatment head(s) through the liquid light guide. In some embodiments,multiple liquid light guides or a bifurcated light guide are used inbilateral systems. Liquid light guides are also more efficient intransmitting light and provide cold light, avoiding the potentialproblem of hot spots. The flexible light guides also provide forvariation in optical head spacing in a bilateral system, and allow for3D movement of the optical head or heads if desired.

In some embodiments, other optical coupling apparatus is used foroptical coupling of components in the ophthalmic treatment systems asalternative to or in combination with the liquid light guide. Thoseoptical coupling apparatus include, but are not limited to mirrors,reflective prisms, refractive prisms, optical gratings, convex lenses,concave lenses, etc. In some embodiments, the treatment light sourcesare provided in one or more treatment heads and treatment light isprojected directly from the light source or sources along an opticalpath to a treatment light output port of the treatment head.

Bilateral Treatment

In some embodiments, the ophthalmic treatment systems is monocular, witha single optical treatment unit including the optical treatment head. Inother embodiments, the ophthalmic treatment systems is bilateral, withtwo optical treatment units adjustably mounted on a support stand fortreatment of both eyes simultaneously. In some embodiments, the opticaltreatment head(s) is configured to focus a UVA or blue light beam on apatient's eye. In other embodiments, the optical treatment head(s)incorporates additional treatment or monitoring devices. In someembodiments, the optical treatment heads are identical but areseparately mounted to allow for adjusting the distance between thetreatment heads. In another embodiment, more than two treatment headsare used in the ophthalmic treatment systems. In some embodiments, theoptical treatment heads allow for independent angular adjustment,adjustment of the distance separating the optical treatment heads,and/or adjustment of the distance between the treatment heads and theeyes. In some embodiments, the optical treatment heads are configured toallow for angular variations as well as distance variations of the atleast one treatment lights. Without wishing to be bound by anyparticular theory, it is contemplated that the independent angle anddistance adjustment allows treatment of strabismus (crossed eyes) and/orallows selective treatment (e.g. crosslinking) of specific areas of thecornea and/or sclera based on pathology of the condition to be treatmentor location of the refractive correction desired.

In some embodiments, the light guide from the light source unit or thewavelength control device is bifurcated to provide two separate lightguide portions which direct UVA or blue treatment light beams from therespective optical treatment heads. Treatment light is projected ontothe cornea and does not require collimation.

The foregoing systems and methods allow the physician to better monitorthe patient's eye during treatment. Some embodiments allow monitoring ofcritical variables during treatment as well as variation of thetreatment criteria, for example switching between UVA and blue orblue-violet light, varying the light intensity, providing a fixationlight to prevent eyes from wandering, utilizing an additional lightsource to prevent the startling effect, varying the beam shape and size,and using a discontinuous/adjustable light projection to allow fortissue reoxygenation. Another technical feature of the system is thatdistance of the optical head from the eye is accurately controlled. Thesystem is easy to set up and use, and allows a high degree of controland customization of treatment to a specific patient condition.

Non-Limiting Examples

Certain embodiments as disclosed herein provide for an ophthalmictreatment system and method.

After reading this description it will become apparent to one skilled inthe art how to implement the present disclosure in various alternativeembodiments and alternative applications. However, although variousembodiments of the present disclosure will be described herein, it isunderstood that these embodiments are presented by way of example only,and not limitation.

FIGS. 1 to 12 illustrate one embodiment of a bilateral system forphotochemical ocular treatment such as corneal and/or scleral collagencross-linking using riboflavin as a photosensitizer. In this embodiment,UVA/blue light is used for the excitation energy. Referring to FIGS. 1and 2, an illumination source unit 10 contains a multi-spectral lightsource 11 that delivers a user-selected excitation wavelength tobifurcated, UV transmissive liquid light guide 18. The light guidesplits into separate light guide outputs 21 and 22 that are connected toillumination intensity adjustment module 30 mounted on a mobile polestand comprised of pole 25 mounted on a base 23 with casters. Othersupport stands of different configuration are used in place of pole 25with base 23 in alternative embodiments. Outputs of module 30 areconnected by light guides 50, 51 to respective left and right opticaltreatment devices or units 150, 151. The right treatment device 151 isdescribed in more detail below in connection with FIGS. 9 and 10. Theleft treatment device 150 is identical to the right treatment device151.

The pole allows attachment and vertical positioning of an adjustablemounting mechanism including articulating arm 24 on which the treatmentdevices 150, 151 are mounted, and provides mounting points forillumination intensity adjustment module 30 and an optical monitoringmodule 40. Modules 10, 30 and 40 are combined in a single unit in otherembodiments. The illumination source unit 10 is shown as separate fromthe mobile stand but is affixed to the stand in another embodiment. Theend of articulating arm 24 connects to rotating arm 27 which furtherconnects to rotating arm 28. The distal end of rotating arm 28 carriesthe two optical treatment devices or units 150, 151 encased in housingunits 260, 261 on adjustable arms 29A, 29B. Each housing unit includesan externally mounted sensor 158, 159. Each housing unit holds in placean optical treatment device 150, 151. Each optical treatment deviceincludes an optical treatment head 81 which directs light onto thepatient's eye, in addition to other components described in more detailbelow in connection with FIGS. 9 and 10. In some embodiments, lightguides 18, 21, 22, 50 and 51 which conduct the excitation energy to eachoptical treatment head are liquid light guides, because the water-basedliquid in the light guide absorbs infrared radiation from the lampsource that could adversely affect tissues. Liquid light guidesgenerally have greater transmission efficiency for UV and visible lightthan fiber bundles while providing greater flexibility to allow foradjustment of the position of each treatment unit. An additional benefitof using liquid light guides is that they are effective in homogenizinglight beams collected from non-homogeneous light sources or reflectors.In alternative embodiments, the light sources and other systemcomponents may be mounted in the respective treatment heads.

FIG. 2 illustrates the layout of the illumination source assembly withan ellipsoidal reflector short-arc lamp 11 as the light source, as inthe first embodiment. In some embodiments this lamp is a 100 wattshort-arc mercury or mercury halide lamp. In a different embodiment,this lamp is a 100 watt short-arc xenon lamp that is characterized by alower UVA output and a greater continuum of high intensity bluewavelength light. Microprocessor 17 controls the opening and closing oflight modulating device (for example, a shutter and/or filter) 12 thateither blocks or allows passage of radiation emitted from the lamp.Light modulating device (for example, a shutter and/or filter) 12 is amirrored aluminum material to reflect radiation away from the opticalpath. The reflective quality of the material prevents a heat buildup onthe shutter and potential transfer of heat to the connecting solenoidassembly. The light modulating device (for example, a shutter and/orfilter) 12 is affixed to a rotary solenoid 160 to affect the opening andclosing operation. Rotary solenoids are high reliability components withnormal lifetimes exceeding 1 million cycles. When light modulatingdevice (for example, a shutter and/or filter) 12 is opened, the lightfrom the lamp reflector is collected by collimating lens 13 and directedto dichroic 45 degree turning mirror 14 that reflects UVA and blue lightin a wavelength range of around 340 nm to 470 nm, while passing infraredradiation. The reflected light from the mirror is collected by focusinglens 15 and directed through one of the filters on filter assembly 16into the input of bifurcated light guide 18. Filter assembly 16 is on aslide mechanism connected to an actuating switch on the front panel. Twonarrowband band pass filters 16A, 16B are mounted on the optics filterassembly 16 and an actuating switch position determines which band passfilter is placed in front of the light guide. In some embodiments,filter 16A is a UVA filter that has a 10 nm bandwidth (FWHM) at 365 nmand filter 16B has a 10 nm bandwidth (FWHM) at 405 nm. Such filters arecommercially available from various optical suppliers.

Various adjustable features of the system described below involve manualinput by an operator at the various units in order to vary operatingconditions, such as intensity adjustment via module 30, selectionbetween the UVA and blue light filters 16A and 16B, and positioning ofthe optical treatment heads. In an alternative embodiment, thesefeatures are adjusted by an operator by input at remote input device orkeyboard, and the controller in this alternative has control outputs tothe selectable filter assembly 16A, 16B, and intensity adjustment module30. An automatic emergency shut off feature is provided in someembodiments.

FIG. 3 illustrates one embodiment of a control panel 110 provided on thefront of illumination source unit 10 including user input devices anddisplay unit 123. In other embodiments, the controller is a standalonedesktop or laptop computer, or a personal digital assistant or the like,with a standard display unit and a keyboard input device for user inputcontrol selections for the various selectable control parameters of thesystem, which is transmitted by wired or wireless communication signalsto control various system components. Panel 110 has a manual wavelengthselection control switch 20 to allow an operator to switch between UVAand blue light, and a manual light modulating device (for example, ashutter and/or filter) control switch 19 to switch between continuousand discontinuous illumination. Soft key inputs 121 below display 123 onthe panel are used by an operator to control the light modulating device(for example, a shutter and/or filter) cycle. The soft keys are switchesthat change function as the display changes.

Referring to FIGS. 1 and 4, the mobile pole stand with the mountedarticulating arm and height adjustment wheel, provides for easypositioning of the optical treatment heads over the patient's eyes.

FIG. 4 is an enlarged top plan view of the articulated arm assembly andtreatment devices 150, 151 of FIG. 1. The height adjustment wheel 26shown in FIG. 1 provides for vertical adjustment of the arm. Lateraladjustment of the optical heads to accommodate different interpupillarydistance is provided by the pivot arms 29A, and 29B on the distal end ofthe articulating arm, as illustrated in FIG. 4. When knob 405 isloosened, both arms 29A and 29B are free to pivot around the center ofarm 28 and knobs 406, 407 are loosened to telescope arms 29A, 29B toadjust the interpupillary distance and to align each optical head withthe respective eyes of a patient. When optical heads on arm 29A, 29B arepositioned over the eyes of the patient, knobs 405-407 are tightened tofix the position. Heads 260 and 261 are still movable at this point anda combined movement of the heads allows for XY axis adjustment of theoptical heads over the patient's eyes for bilateral operation. Knobs 408and 409 are tightened to secure the position of the optical heads overthe patient's eyes. In alternative embodiments, the manual positioningknobs are eliminated and another system is provided for vertical andhorizontal positioning of the treatment heads.

In alternative embodiments, the manual positioning knobs are eliminatedand a remotely controlled drive system is provided for vertical,horizontal, and angular positioning of the treatment heads. X, Y and Zdirection positioning are then controlled remotely by the operator via acomputer input device, touch screen or the like, or are carried outautomatically on entry of patient eye parameters by the physician, forexample as described below in connection with the embodiment of FIGS. 23to 29.

In the ophthalmic treatment system of FIGS. 1 to 11, the at least onetreatment light beam of each optical head is directed concentric to theoptical axis passing through the center of the cornea to the center ofthe lens in some embodiments. It is desirable in some circumstances toposition the light beam on an optical axis different than thecorneal-lens optical axis. For example, if the apical distortion fromkeratoconus is in the inferior portion of the cornea, it is desirable toplace the optical axis of the illumination beam concentric with thecentral axis of the apical distortion in some embodiments to maximizethe radiation concentrically around the apical distortion. FIGS. 8A and8B illustrate one example of the apical distortion of keratoconuscompared to a normal cornea. FIG. 8A illustrates an eye 500 with anormal cornea 502, with the dotted line 504 representing the opticalaxis passing through the center of the cornea. FIG. 8B illustrates eye500 with keratoconus causing an off-axis conical distortion andresultant thinning of the cornea at 506. This requires an XYZpositioning flexibility for the optical head, and this is achieved inone embodiment by the mechanical arrangement shown in FIG. 4 asdescribed above.

The output light intensity adjustment for each eye in the system ofFIGS. 1 to 17 is accomplished using the intensity adjustment module 30illustrated in layout view in FIG. 7. Mechanical brackets are affixed tothe output light guides and these brackets are connected to commercialscrew-driven linear slides 31 and 32. The bifurcated input light guideends 21 and 22 are fixed at the bottom of the module. Turning theexternally accessible knobs on slides 31 and 32 clockwise advances thedelivery light guides 50 and 51 toward the input light guides andincreases the intensity of the output. Likewise, turning the knobs in acounterclockwise direction reduces the intensity. The output is measuredby using an external hand held radiometer under the output optics.Appropriate radiometers for UVA or blue light are commercially availablefrom a variety of sources. Adjustment of the output of each optical headwithin 0.01 mw/cm2 is obtained in this embodiment. In anotherembodiment, adjustable neutral density filters are placed between theinput and output light guides but these filters are often subject tolong term UVA deterioration. FIG. 7 illustrates the maximum intensityadjustment for excitation light guide 51 and the minimum intensityadjustment for excitation light guide 50.

In the illustrated embodiment, a manually operable switch 55 allows auser to convert from bilateral to monocular operation. Switch 55 isconnected to light modulating device (for example, a shutter and/orfilter) 56. In the position of light modulating device (for example, ashutter and/or filter) 56 as shown in FIG. 7 the light entering fromlight guide 21 is blocked from entering the delivery light guide 51 andthe instrument is set for monocular operation. When the switch isrotated from this position, the light modulating device (for example, ashutter and/or filter) rotates out of the light path and closes amicroswitch. Light now travels to both output heads and the closedmicroswitch completes a circuit to light an LED on top of the modulealerting the user that the instrument is in bilateral mode. Inalternative embodiments, the manual switch is replaced by a remotecontrol device such as a computer module with a user control input ortouch screen for switching between bilateral or monocular operation. Thesame control input is used in some embodiments to enter commands to varyother adjustable features of the system, such as the excitation energyfrequency, intensity, continuous or discontinuous illumination,treatment period, treatment head height, separation, and angle, and thelike.

One of the optical treatment devices 151 is illustrated in more detailin FIGS. 5, 9 and 10. As illustrated, each optical treatment devicecomprises optical treatment head 155 vertically mounted on support 154at the end of the respective arm 29A or 29B, and optical collectiondevice 158 also mounted on support 154 adjacent the optical treatmenthead 155, as illustrated in FIG. 9. Treatment head 155 incorporates anoptical mask or reticle holder 80 in which a selected reticle or mask 90may be positioned for controlling shape and/or size of the outputtreatment beam projected from treatment head 155 via projection optic orlens 81 located at the output port of the treatment head. Aiming orpositioning apparatus 65, 66 mounted in each optical treatment unit 150and 151 assists an operator in positioning the projection optic or lens81 at a desired working distance from the cornea. In the embodiment ofFIGS. 5, 9 and 10, the aiming devices 65, 66 are laser diodes. Thedistance of optic 81 from the cornea is determined to be equal to thedesired working distance when the two aiming beams from laser diodes 65and 66 coincide with each other as a single spot on the patient's eye.If the aiming beams do not cross at the eye, the height adjustment knob26 on the articulating arm can move the optical heads up or down untilthe beams coincide at the correct position. This provides a moreaccurate method for positioning the optical heads at a predetermineddistance relative to the patient's eyes.

In one embodiment, filters 85 or 86 may be selectively positioned in thepath of the aiming beams emitted from aiming devices 65, 66 viamechanical slide 84 (see FIG. 10). This may provide a secondary use tothe aiming beams for providing red light phototherapy to ameliorateoxidative damage to the cells. In another embodiment, the aiming devices65, 66 may be red or green light laser diodes with no filters in theoutput path.

In some embodiments, the ophthalmic treatment system also includesmonitoring system 40 for the photoluminescence emitted from theriboflavin interaction with UVA/blue light, using optical collectiondevice 158 as illustrated in FIG. 9. This photoluminescence consists offluorescence from the riboflavin photonic emission from the S1 to S0state and phosphorescence emitted from the triplet riboflavin state.These photoluminescent emissions allow measuring of riboflavinconcentration in the eye (e.g., the cornea or sclera), a relativemeasure of the depth of penetration of the riboflavin into the stroma, arelative measure of the lateral homogeneity of the riboflavin and arelative measure of the oxygen utilization and triplet state formation.The reaction of riboflavin and UVA/blue radiation involves twoelectronically excited states of riboflavin. When ground state S0(unexcited riboflavin) absorbs UVA/blue light it transitions into anexcited state called the S1 state. From the excited S1 state, themolecule loses its energy by two mechanisms. The first mechanism is therelaxation back to the ground state by emitting a photon of light in aprocess called fluorescence. The peak fluorescence of riboflavin isabout 525 nm. The average quantum yield for riboflavin in aqueoussolutions is about 0.3, meaning that the ratio of photonsemitted/photons absorbed is about 0.3. The second mechanism forrelaxation from the S1 state is called the formation of tripletriboflavin and this is accomplished by a mechanism called intersystemcrossing. The triplet state of riboflavin imparts energy to molecularoxygen and creates singlet oxygen for cross-linking. From this tripletstate the riboflavin molecule can react and give up the excess energy tooxygen or water, or it can phosphoresce to the ground state. Thephosphorescence of triplet riboflavin occurs at around 605 nm. Sincephosphorescence is a direct measure of the active species that createssinglet oxygen, optical collection device 158 and optical monitoringdevice 40 of FIG. 11 are configured to monitor both the fluorescent andphosphorescent signals.

Optical collection device 158 of FIG. 9 comprises light collection lens83 and bifurcated light guide 70 which receives the light collected bylens 83. This bifurcated light guide has one single end that splits intotwo output ends 70A, 70B. The lens 83 is directed to the center of theeye (e.g., the cornea or sclera) treatment zone and receives thephotoluminescent emissions from the eye (e.g., the cornea and/or sclera)and focuses these emissions to the proximal or receiving end 185 of thesingle-ended portion 70 of the bifurcated light guide. The light guidein some embodiments provides 50% of the proximal input light into eachof the two distal light guide portions 70A, 70B. The distal portions ofthe light guides are routed to the optical monitoring module 40 shown inlayout view on FIG. 11. The optical heads or ends 185 on each of thelight guides 70, 71 of the treatment devices 150 and 151 receive thephotoluminescent emissions from the irradiated corneas and/or scleras ofthe patient's left and right eyes, and the emission light is transmittedby light guides 71 and 70, respectively, into left eye guide portions71A, 71B and right eye guide portions 70A, 70B. The photoluminescentemission from each eye includes both fluorescence and phosphorescencedue to different types of riboflavin interactions, as discussed indetail below. The emission light is directed onto filters 42 and 43 forseparating fluorescence emission from phosphorescence emissions for eacheye, as illustrated in FIG. 11. Filter 42 is a narrowband band passfilter with a center wavelength of 525 nm-535 nm to capture the peak ofthe fluorescence emission from the riboflavin. Filter 43 is a narrowbandband pass filter centered at 600 nm-605 nm to capture the peak of thephosphorescence of the triplet riboflavin. By splitting the emissionscollected from each eye being treated, both the phosphorescence andfluorescence for each eye are monitored in some embodiments. Thefiltered emission light from each light guide is directed onto arespective sensor 41, which comprises a PIN silicon photodiode 41 thatincorporates an integral preamplifier or thermoelectric cooling, and theoutput voltage of the photodiode is transmitted to high impedanceamplifier 45 for conversion of the photonic energy into voltage.Alternatively, items 41 and 45 are purchased as an integral unit fromcommercial sources such as Thorlabs and are capable of detection ofsignals as small as a few femtowatts (10⁻¹⁵ watts).

FIG. 12 illustrates one embodiment of a hand held dodging fixture ortool 250 that may be used to provide a relative measure of the lateraldispersion of riboflavin in the eye. Tool 250 has a handle 202 with aplastic holder 201 at one end which holds a UV transparent/visibleblocking glass with a 3 mm hole drilled at its center. Commercialglasses such as Schott UG 11 and Schott BG 4, respectively, are suitablefor use with UVA and blue treatment light, respectively. The onlyemitted light to reach the collection device 158 is via the hole in thecenter of glass 200. The dodging fixture may be held over the centralcornea and the resultant fluorescence reading from the opticalmonitoring module 40 then reflects emissions from only a limited area ofthe cornea. The fixture can be moved over different areas of the corneato obtain readings relative to the central area and other areas. Thistool can therefore provide a relative quantitative measure of lateraldispersion of riboflavin in the eye. If readings show that moreriboflavin than the peripheral areas, the physician may choose to waitfor a longer period for the riboflavin to disperse, or may take otheraction to promote dispersion, e.g. placing a warm cloth over the closedeye for a few minutes.

In some embodiments, the phosphorescence of the riboflavin triplet stateis used to monitor the efficiency of the reaction particularly withrelation to singlet oxygen formation. Each eye is monitored for bothfluorescence and phosphorescence using optical collection devices 158and photoluminescence monitoring unit 40, as described above. The lightmodulating device (for example, a shutter and/or filter) 305, 315 inFIGS. 13 and 14 provides discontinuous light projection and theoperation of the light modulating device (for example, a shutter and/orfilter) cycle in one embodiment is directed by the operator by the softkey inputs on the control panel shown in FIG. 3.

FIG. 6 illustrates a perspective view of the right hand opticalcollection device 158 in housing 264 with optical collection node 83encased by head unit 280. Housing unit 264 is attached to casing unit260 which envelopes the right hand optical treatment device shown inFIGS. 5, 9, and 10. Mounting unit 262 is attached to the treatment endof casing unit 260.

Mounting unit 262 is fitted in each corner with holes 271-274 such thatanother plate is affixed to the unit with a screw and nut, or likemethod.

FIGS. 1 and 13-18, illustrate several embodiments of a bilateral systemfor discontinuous/adjustable/patterned photochemical ocular treatmentsuch as corneal and/or scleral collagen cross-linking using riboflavinas a photosensitizer. In those embodiments, UVA/blue light is used forthe excitation energy. Referring to FIGS. 1 and 2, an illuminationsource unit 10 contains a multi-spectral light source 11 that delivers auser-selected excitation wavelength to bifurcated, UV transmissiveliquid light guide 18. The light guide splits into separate light guideoutputs 21 and 22 that are connected to illumination intensityadjustment module 30 mounted on a mobile pole stand comprised of pole 25mounted on a base 23 with casters. Other support stands of differentconfiguration are used in place of pole 25 with base 23 in alternativeembodiments. Outputs of module 30 are connected by light guides 50, 51to respective left and right optical treatment devices or units 150,151. As described in detail above, the ophthalmic treatment system alsoincludes monitoring system 40 for the photoluminescence emitted from theriboflavin interaction with UVA/blue light, using optical collectiondevice 158 as illustrated in FIG. 9, and shown encased in housing unit264 in FIG. 6. The left treatment device 260 is described in more detailbelow in connection with FIGS. 13 to 18. The right treatment device 261is identical to the left treatment device 260.

FIG. 13 illustrates a manually operated mechanical light modulatingdevice (for example, a shutter and/or filter) housed in mounting unit300 which is affixed to treatment mounting unit 262 at points 271-274,with a screw and nut, or like method, through points 301-304. When lever306 is moved to the down position, mechanical light modulating device(for example, a shutter and/or filter) 305 will open, allowing UVA/bluelight from treatment head 81 to pass unobstructed onto the treatmentarea. Mechanical light modulating device (for example, a shutter and/orfilter) 305 remains open until the treating physician deems it necessaryto provide a period of discontinued light projection. The determinationis assisted by data from optical collection device 264 mounted totreatment head casing 260, and connected to monitoring system 40,FIG. 1. Light collection guide 71 is not shown in this view for purposesof clarity but the receptacle for this light guide connects to the rearend of optical collection device 264. The mechanical light modulatingdevice (for example, a shutter and/or filter) remains open for a periodof photochemical crosslinking lasting 15 seconds to 10 minutes. Lever306 is then moved to the up position, closing mechanical lightmodulating device (for example, a shutter and/or filter) 305. Whenmechanical light modulating device (for example, a shutter and/orfilter) 305 is closed, no UVA/blue light from optical treatment head 81will reach the treatment area. The mechanical light modulating device(for example, a shutter and/or filter) remains closed for a period of 15seconds to 10 minutes in some embodiments to allow for tissuereoxygenation. The process of opening and closing mechanical lightmodulating device (for example, a shutter and/or filter) continues asmany times as the physician deems necessary.

FIG. 14 illustrates an automatic mechanical light modulating device (forexample, a shutter and/or filter) housed in mounting unit 310 which isaffixed to treatment mounting unit 262 at points 271-274, with a screwand nut, or like method, through points 311-314 (313 and 314 not shown).Automatic control unit 316 is affixed to mounting unit 310, andconnected by cable 317 to UVA light source housing and control unit 10,FIGS. 1, 2. When treatment begins, mechanical light modulating device(for example, a shutter and/or filter) 315 is opened by control unit316, allowing UVA light from treatment head 81 to pass unobstructed ontothe treatment area. The mechanical light modulating device (for example,a shutter and/or filter) 315 remains open for a treatment session of 15seconds to 10 minutes, off-set by periods of discontinuous illuminationlasting 15 seconds to 10 minutes. When mechanical light modulatingdevice (for example, a shutter and/or filter) 315 is closed, no UVA/bluelight from optical treatment head 81 reaches the treatment area.Duration of discontinuous illumination, and number of treatment cyclesis set on display control unit 110, FIG. 3. In one embodiment, UVA orblue light may be provided in a fractionation cycle of 15 seconds ON/15seconds OFF, and in this case the shutter is opened and closedautomatically.

In another embodiment, automatic control unit 316 affixed to mountingunit 310 is connected by cable 317 to optical collection monitoringsystem 40, FIG. 1, 11. When treatment begins, mechanical lightmodulating device (for example, a shutter and/or filter) 315 is openedby control unit 316, allowing UVA light from treatment head 81 to passunobstructed onto the treatment area. The mechanical light modulatingdevice (for example, a shutter and/or filter) remains open until amicroprocessor housed in monitoring system 40 (not shown), determinessinglet oxygen levels are sufficiently depleted. Light modulating device(for example, a shutter and/or filter) 315 is then automatically closed,allowing no UVA/blue light from optical treatment head 81 to reach thetreatment area. Light modulating device (for example, a shutter and/orfilter) 315 remains closed for a period of time lasting 15 seconds to 10minutes. This process is repeated until treatment is complete.

FIG. 15 illustrates a manually or automatically controlled dimmer unit320 mounted on a mobile pole stand comprised of pole 25 mounted on abase 23 with casters. Other support stands of different configurationare used in place of pole 25 with base 23 in alternative embodiments.During treatment, dials 321-324 are turned manually to increase ordecrease the intensity of the UVA/blue light administered to thetreatment areas. When treatment begins, gradually increasing from 0% to100% intensity will mitigate the startling effect. The UVA/blue lightremains at 100% intensity until the administering physician deems itnecessary to provide a period of discontinued UVA/blue light projection.This determination is assisted by data from optical collection device264 mounted to treatment head casing 260, and connected to monitoringsystem 40. The UVA/blue light remains at 100% intensity for a period oftime lasting 15 seconds to 10 minutes. Knobs 321-324 are then engaged togradually decrease the intensity of the UVA/blue light from 100% to ator near 0%, in order to mitigate the startling effect. At or near 0%intensity, little or no UVA/blue light from optical treatment headsreaches the treatment areas. The intensity remains at or near 0% for aperiod of 15 seconds to 10 minutes to allow for tissue reoxygenation.The process of increasing and decreasing the intensity continues as manytimes as the physician deems necessary.

In another embodiment, intensity is increased and decreasedautomatically by a microprocessor-controlled dimmer switch housed indimmer unit 320 (not shown). The microprocessor controlled dimmer switchis connected by cable 325 to UVA light source housing and control unit10, FIGS. 1,2. When treatment begins, light intensity is graduallyincreased to 100% allowing UVA light from treatment head 81 to passun-dimmed onto the treatment area. The light remains un-dimmed for atreatment session lasting 15 seconds to 10 minutes, off-set by period ofdiscontinuous illumination wherein the light is slowly reduced inintensity from 100% to at or near 0%. Light intensity remains at or near0% for 15 seconds to 10 minutes. When light intensity is at or near 0%,no or little UVA/blue light from optical treatment head reaches thetreatment area. Duration of discontinuous illumination, and number oftreatment cycles are set on display control unit 110, FIG. 3.

In another embodiment, during treatment, intensity is increased anddecreased automatically by a microprocessor-controlled dimmer switchhoused in dimmer unit 320 (not shown). The microprocessor-controlleddimmer switch is connected by cable 325 to optical collection andmonitoring system 40. When treatment begins, UVA/blue lightautomatically increases intensity from at or near 0% to 100%. The lightintensity remains at 100% until a microprocessor housed in opticalmonitoring system 40 (not shown), determines singlet oxygen levels aresufficiently depleted. Dimmer unit 320 then automatically reducesUVA/blue light intensity from 100% to at or near 0%, allowing noUVA/blue light from optical treatment heads to reach the treatment area.Light intensity remains at or near 0% for a period of time lasting 15seconds to 10 minutes. This process is repeated until treatment iscomplete.

FIG. 16 illustrates a manually operated UVA/blue light filter housed inmounting unit 330 which is affixed to treatment mounting unit 262 atpoints 271-274, with a screw and nut, or like method through points331-334. UVA filters 336 are held in place by housing units 335 which isslid into mounting unit 330 such that UVA filters 336 are directly inthe path of the UVA/blue light emitted by treatment head 81. When slides335 are removed from mounting unit 330, this allows UVA/blue light fromtreatment head 81 to pass unobstructed onto the treatment area. Theslides remain free of the mounting unit until the treating physiciandeems it necessary to provide a period of discontinued light projection.This determination is assisted by data from optical collection device264 which is mounted to treatment head casing 260, and connected tomonitoring system 40, FIG. 1. Light collection guide 71 is not shown inthis view for purposes of clarity but the receptacle for this lightguide connects to the rear end of optical collection device 264. Slides335 remain clear of mounting unit 330 for a period of time lasting 15seconds to 10 minutes. Slides 335 are then inserted into mounting unit330. When slides 335 are inserted into mounting unit 330, no UVA/bluelight from optical treatment head reaches the treatment area. The slidesremain in the mounting unit for a period of 15 seconds to 10 minutes toallow for tissue reoxygenation. The process of inserting and removingthe slides continues as many times as the physician deems necessary.

FIG. 17 illustrates an automatically operated UVA/blue light filterhoused in mounting unit 340 which is affixed to treatment mounting unit262 at points 271-274, with a screw and nut, or like method, throughpoints 341-344. Automatic control unit 346 is affixed to mounting unit340, and connected by cable 347 to optical collection monitoring system40, FIG. 1, 11, 15. UVA/blue light filters 345A are housed inretractable units 345B controlled by unit 346. When treatment begins,slides 345B are retracted, allowing UVA/blue light from treatment head81 to pass unobstructed onto the treatment area. Filters 345B remainretracted until a microprocessor housed in monitoring system 40 (notshown), determines singlet oxygen levels are sufficiently depleted.Automatic control unit 346 then slides filters 345B into the path oflight emitted from treatment head 81. When UVA/blue light filters are inthe path of the UVA/blue light emitted from treatment head 81, noUVA/blue light reaches the treatment area. Filters 345B remain in thepath of the light emitted from treatment head 81 for a period of 15seconds to 10 minutes. This process is repeated until treatment iscomplete.

In another embodiment, an automatically operated UVA/blue light filterunit housed in mounting unit 340 is affixed to treatment mounting unit262. Automatic control unit 346 is affixed to mounting unit 340, andconnected by cable 347 to UVA light source housing and control unit 10,FIGS. 1,2. When treatment begins, slides 345B are retracted, by controlunit 346 allowing UVA light from treatment head 81 to pass unobstructedonto the treatment area. The slides remain retracted for a treatmentperiod of 15 seconds to 10 minutes, off-set by periods of discontinuousillumination where the slides are engaged, lasting 15 seconds to 10minutes. When UVA/blue light filters 345A are obstructing the path oflight emanating from treatment head 81, no UVA/blue light reaches thetreatment area. Duration of discontinuous light projection, and numberof treatment cycles is set on display control unit 110, FIG. 3

FIG. 18 illustrates a rotating UVA/blue light filter assembly, 350.Filter discs 355A, 355B, 355C, or 355D allow for variable treatmentareas. Filter disc 355A has a UVA transparent spot 170 offset from thecenter of the disc, filter disc 355B has a UVA transparent region 171 ofaround 90 degrees of the circular disc area with the rest of the discbeing solid or black, filter disc 355C has a UVA transparent region 172of about 30 degrees with the rest of the disc being solid, and filterdisc 355D has a transparent region of 180 degrees with the rest of thedisc being solid. Filter discs with other arrangements of UVAtransparent and solid areas may be provided in other embodiments. Filterdiscs are housed in rotating disc assembly 359, held in place by pin361, and rotated by gear assembly 358. Light filter assembly 350 isaffixed to treatment mounting unit 262 at points 271-274 (not shown),with screw and nut, or like method, through points 351-354. Automaticcontrol unit 356 is affixed to filter assembly 350, and connected bycable 357 to UVA light source housing unit 10, FIGS. 1, 2 (not shown).Before treatment begins, a treatment disc 355A, 355B, 355C, or 355D isinserted into housing unit 359. When treatment begins, disc is rotatedin a circular motion. Selected disc allows UVA/blue light to passthrough the transparent portion, and no UVA/blue light to pass throughthe solid portion. The period of time for disc to make one full rotationis a treatment cycle. Duration of treatment cycles is set on displaycontrol unit 110, FIG. 3. In the case of disc 355A, an annular treatmentarea is provided by one full rotation of the disc.

FIG. 19 illustrates a perspective view of a UVA/blue light treatmenthead and casing with holder 196 for changeable irradiation patternreticle or mask 190 with handle 195 for positioning purposes. FIG. 20illustrates some examples of additional reticles or masks 186, 188, 189and 191 to 194 which have apertures or windows of UVA and/or blue lighttransparent material providing a variety of different light distributionpatterns and sizes desired by the physician, allowing more light toreach selected parts of the treatment area. For example, reticle 191 hasan oval aperture, reticle 192 has a slit shaped aperture, reticle 193has a square shaped aperture, reticle 194 has an annular ring shapedaperture, reticle 186 has two apertures of different shapes, reticle 188has a pseudo tilde or “squiggly line” aperture, and reticle 189 has acrescent shaped aperture. The squiggly line aperture of reticle 188 maybe thicker or wider in one segment, as illustrated, or may be of thesame proportions throughout. As illustrated in reticle or mask 186, twoor more apertures of the same or different shapes may be provided wheredifferent areas of the eye are to be treated simultaneously. Additionalmasks with apertures or patterns of apertures of different shapes andsizes may also be provided in a patterned mask kit, to provide expandedcustom treatment options.

Although the mask 190 is positioned in holder 196 by hand in theembodiment of FIG. 19, alternative embodiments may have an automaticcontrol unit affixed to housing 260, and connected by cable to acontroller or microprocessor. The reticles or masks of differentaperture sizes and shapes are housed in retractable units controlled bythe automatic control unit. When treatment begins, the operator selectsa pattern at an input device (for example as described below inconnection with the embodiment of FIGS. 23 to 28) and the automaticcontrol unit slides the selected reticle or mask into the path of lightemitted from treatment head 81. This may be used in conjunction with ashutter for discontinuous treatment as described above.

FIG. 21 illustrates a perspective view of a UVA/blue light treatmenthead and casing 260 with a secondary non-treatment light source oranti-startle light source 196. In some embodiments, the secondary lightsource is powered on in such a way as to mitigate dramatic changes inlight seen by the patient as the UVA/blue light is filtered, blocked, ordimmed. The secondary light source is of a wavelength and intensityfitting to reduce the startling effect a patient experiences as a resultof dramatic changes in light intensity or color. In one embodiment,light source 196 is a green LED light. The secondary light source may beaffixed to the treatment head casing in such a way that it is visible bythe patient during periods of discontinuous illumination.

FIG. 22 illustrates one embodiment of a fixation light 197 in housing198 attached to a supporting arm or gooseneck 200 which can be manuallyadjusted so that the fixation light is positioned over the patient'seyes 199 at a distance of 10 to 24 inches or greater, and serve as afocus point in order to maintain a stable treatment area. Fixation lightmay be controlled by a controller or microprocessor via cables extendingthrough arm 200 to the light. The fixation light is a red light or anyother light in the visible spectrum. The fixation light also performs aperiodic blink or auditory cue to remind the patient to focus theirattention on the fixation point in some embodiments. In anotherembodiment, each treatment head has its own separate fixation light.

FIGS. 23 to 30 illustrate an ophthalmic treatment device or system 400according to another embodiment in which various control parameters arecontrolled remotely by the operator or physician via a computer inputdevice, touch screen or the like, or are carried out automatically onentry of patient eye parameters by the physician. Treatment device 400includes a control unit 401 mounted on a support stand having a wheeledbase 410 and a telescoping pole 402 extending upwardly from the base andadjustable via rotatable telescoping pole lock 403 at a desired height.The control unit 401 comprises an enlarged housing 404 at the top ofpole 402 and a touch screen user interface unit 405 mounted on top ofhousing 404. Treatment heads 406 are supported on respective flexiblecable arms or goosenecks 412 extending from housing 404 and componentswithin heads 406 are linked to control unit 401 via a wirelessconnection or wired connection through arms or goosenecks 412, asdescribed in more detail below in connection with FIGS. 27 to 30.Fixation light 198 of FIG. 22 is also supported on stand 402 viagooseneck 200 extending from cable junction 403 and adjustable cable arm414 extending from junction 403 to control unit 401.

As best illustrated in FIGS. 26 to 28, in one embodiment each treatmenthead 406 comprises a generally elongate outer housing 411 secured togooseneck 412 at one end and having a lower, generally flat wall 413 inwhich a large UVA/blue light output port 426 is located, along with twoadjustment or positioning light output ports 424A and 424B foradjustment or positioning light, and a photoluminescence monitor inputport 425 (see FIG. 26). As illustrated in FIGS. 27 and 28, one side ofthe housing contains the optical system or light path from UVA and/orblue light emitter or LED 428 to the UVA/blue light output port 426. Theother side of the housing contains printed circuit boards 434 and 435carrying red and green light adjustment LEDs directed to respective redand green light positioning output ports 424A and 424B, respectively,along with associated control circuitry. A third printed circuit board(PCB) 436 carries a photoluminescence sensor or monitor 436 (FIG. 30)which receives input from input port 425. The output fromphotoluminescence monitor 436 is communicated via leads in arm 412 tothe controller or microprocessor 418 in the control housing 404 at theupper end of stand 400.

As illustrated in FIGS. 27 and 28, the UVA or UVA/blue light source 428has an output directed through light homogenizer or light guide 429along a light path through lens 438 to 90 degree mirror 440, whichdirects the light downward through output port 426 of FIG. 26. A mask orreticle wheel 432 is rotationally mounted on shaft 433 in the lightpath. As illustrated in FIG. 29, reticle wheel 432 has a series ofopenings of different diameter around its periphery. Part of theperiphery of wheel 432 extends out through a slot 431 in housing toallow the wheel to be turned manually in order to align a selectedopening with the UVA or UVA blue light path. In one embodiment, theopenings in the pupil or reticle wheel allow adjustment of the beam spotsize in the range from around 9 to 12 mm. In an alternative embodiment,a drive motor, stepper, or external gear wheel (as in FIG. 18) may beprovided for moving wheel 432 according to a user input at userinterface 416, which may be a touch screen as illustrated in FIG. 25 ora keypad. Additionally, a plurality of reticle wheels with openings ofdifferent sizes and shapes, such as the shapes shown in FIG. 20 andother alternative shapes, may be provided for selective placement in thelight path in place of wheel 432. The reticle wheel may be replacedmanually or automatically under the control of microprocessor 418, forexample as described above in connection with FIGS. 17 and 18. Thus,beam size and shape may be modified in order to produce a selected sizeand pattern of the treatment light projection onto an eye.

Although the treatment LED or light source in this embodiment is asingle LED, an array of multiple light sources or LEDs, e.g. two or moreLEDs, may be provided as the UVA, blue or UVA/blue light source inalternative embodiments. As illustrated in FIG. 28, an anti-startlelight source 450 is positioned in the housing directly above UVA LED428, and light output from source 450 is directed via light guide orbeam homogenizer 451 and lens 439 in a path parallel to the treatmentlight beam up to 90 degree mirror 441, which directs the anti-startlelight beam downwards through output port 426. In one embodiment, theanti-startle light source is a green light LED but it may be a visiblelight of other colors in alternative embodiments.

In one embodiment, microprocessor 418 is programmed to turn the UVA orUVA/blue light source or LED on and off at predetermined intervals, toprovide discontinuous UVA treatment light. The green anti startle LED450 is turned on when the UVA treatment light is off, for the reasonsstated above in connection with the embodiment of FIG. 21. In oneembodiment, the ON and OFF periods for discontinuous UVA treatment maybe 15 sec. ON, 15 sec. OFF, and the total treatment time may be of theorder of 20 to 30 minutes, with an intensity or irradiance of 3-4 mW/cm². In one embodiment, the irradiance or intensity is gradually increasedat the start of each ON period, and gradually dimmed at the end of eachON period down to 0.1 or 0.2 mW/cm², and is not completely turned offbefore it is replaced by the green anti-startle light. Using thissystem, a UVA light of wavelength from 350 to 400 nm or UVA/blue lightof wavelength of from 365-420 nm for deeper cross-linking is used todeliver an irradiance of from 3 to 30 mW/cm2, in discontinuous cyclesvariable from 1 second to 1 minute or more, and through a selectedreticle or pupil wheel with apertures that provide a specific lightdistribution pattern to cross-link selected areas of the cornea and/orsclera. However, all of these parameters (frequency and length oftreatment light exposure periods, irradiance, total treatment time, beamsize, beam shape) may be varied based on the particular treatmentrequirements, and some or all of the treatment parameters may also bevaried automatically based on feedback to the microprocessor 418 fromthe photoluminescense monitoring device 436.

In this embodiment, X, Y and Z positioning of the treatment heads may becarried out manually by the operator or physician using the flexiblegoosenecks, with the assistance of the red and green positioning LEDs424A and 424B for locating each head at the desired height above the eyeand with the treatment beam aligned with the desired position on theeye. By providing two angled alignment beams of different colors, it iseasier for the operator to determine when the treatment head is at thedesired working distance from the eye with the UVA/blue light outputport aligned with the desired treatment area, when the red and greenaiming beams coincide with each other as a single yellow spot on theeye. In other embodiments, a robotic positioning system controlled bythe microprocessor may be used to position the treatment heads.

In one embodiment, the UVA light source was a NCSU033B UV LEDmanufactured by Nichia Corporation of Tokushima, Japan, but other UVALEDs with similar properties may be used in other embodiments. The greenanti-startle LED, red and green positioning LEDs, and red fixation LEDare selected to have flux densities well below the maximum safe orallowable flux onto the pupil of an eye. The green and red LEDs in oneembodiment were parts LT T673 NISI 25 Z (green LED) and LR T67F-U1AA-1-1manufactured by Osram GmbH of Munich, Germany, but other red and greenLEDs with similar properties may be used in other embodiments.

FIG. 30 is a block diagram of the control system for the treatmentdevice of FIGS. 23 to 30. As illustrated, microprocessor 445 controlsthe on/off treatment cycle or discontinuous irradiation 445 of the UVAor UVA/Blue light source or light source array 428, and also controlsturning on and off of the green anti-startle LED 450 so that it is ONwhen the UVA light is OFF. It should be understood that the UVAtreatment LED is not necessarily turned off completely during thetreatment OFF periods, but may be turned down to a minimal irradiance orintensity during these periods. The system also includes an irradianceor dimmer control 446 which controls irradiance level based on inputfrom controller 418 in response to programmed instructions or input fromthe operator. UVA/blue output sensor or monitor 430 detects irradiancelevel and provides a feedback input to controller 418. The UV or UVAbeam size and shape is controlled by selected reticles in pupil wheel orreticle holder 432 located between the UVA LED and the output port 426as described above in connection with FIGS. 28 and 29, and selection ofthe appropriate size and shape opening for alignment with the LED outputmay be performed manually by the operator at the start of eachtreatment, or automatically via an input from microprocessor orcontroller 418.

The red and green positioning LEDs 424A and 424B are also controlled bymicroprocessor 418 and may be switched on by user input on the touchdisplay screen, for example, when positioning the treatment heads. Oncepositioning is completed, the positioning LEDs are turned off. Outputfrom the photoluminescence monitor 436 is also provided tomicroprocessor 418 and may be displayed on the display screen or touchscreen 416 for use in determining various treatment parameters includingamount of riboflavin solution to be added, variation of ON/Off treatmentcycles, and the like. Fixation light or LED 199 is switched on at alltimes during treatment so that the patient can focus their eyes on thelight and maintain a static or substantially static

The systems and methods described above allow for bilateral or monocularphotochemical cross-linking of corneal and/or scleral collagen employingselectable UVA/blue light as the excitation source and riboflavin as thephotosensitizer. One embodiment of the system has an illumination sourcewith multi-spectral capability, light guides for delivery of light tobilateral optical heads for projection onto the corneal and/or scleralsurface of both eyes simultaneously, and in this system the light sourceis an Hg or Xe short arc lamp. The light source is connected to thetreatment head or heads via liquid light guides, which produces improvedhomogeneity in the light beam. In another embodiment, the system hastreatment heads each incorporating one or more treatment light sourcesand optics for directing a treatment beam from the light source out ofan outlet port which may be positioned to direct the treatment beam ontoa patient's eye. In this system, the light sources may be singlewavelength or limited wavelength light sources such as LEDs or laserdiodes.

The image projection optics are designed to produce a relatively largeworking distance between the treatment head and the eye, which is atleast 50% greater than the working distance in prior art cornealtreatment systems. This provides better visualization for the surgeon aswell as better access for discontinuous or diffusion augmentationtechnique, described in detail above. In some embodiments, provision ismade for an adjustable working distance.

In some or all of the foregoing embodiments, a highly oxygenated topicalsolution is placed on the cornea and/or sclera for stromal reoxygenationduring cross-linking treatment, such as a solution containing iodide ionor a lipid or oil-based fluid that is pre-oxygenated at a high oxygenpartial pressure. In another alternative, a hydrogen peroxide reducingagent or solution is applied to the eye which converts hydrogen peroxideproduced in the stroma during irradiation of the eye into oxygen andwater. Suitable reducing agents for application to the eye for thispurpose are topical solutions containing iodide ion or the enzymecatalase. These agents are added to any standard riboflavin solution oras a separate solution applied to the cornea and/or sclera duringphotochemical treatment in some embodiments. In some or all of theforegoing embodiments, the iodide is kept in ionized (I⁻) form.

In some embodiments, the disclosed treatment system treats conditionsincluding iatrogenic effect or the prevention of iatrogenic effect, fromsurgical intervention such as cataract surgery or corneal grafting,refractive intervention such as Laser-Assisted in Situ Keratomileusis(LASIK) or photorefractive keratectomy (PRK), radial keratotomy (RK), orprosthesis, corneal inlays or onlays, or medications, or the cause ofcorneal or scleral weakness can be congenital, idiopathic or due tomicrobial causes or trauma.

In some embodiments, the disclosed treatment system treats keratoconus,ectasia, Terrien's marginal degeneration, pellucid marginaldegeneration, and corneal melting or ulcer, or normal or weakenedcorneas that require from 0.25 to 4.0 diopters or more of refractivecorrection for the treatment of myopia, hyperopia, astigmatism or otherrefractive errors of the eye, or corneal inflammatory disorders such asinfectious keratitis and/or corneal ulcers.

A non-limiting example for using the ophthalmic treatment systems totreat a patient with keratoconus is provided as follows. After topicallocal anesthesia of the eye, a proprietary sponge (e.g. the spongedisclosed in U.S. patent application Ser. No. 14/275, 192 filed on May12, 2014, the contents of which are incorporated herein by reference) isused to gently wipe the surface of the eye to remove tears, mucous,lipids, and other macromolecules, and to mildly disrupt but not removethe epithelium. A surgical sponge is then placed over a selected portionor the entire surface of the cornea and/or sclera, onto which a 0.1% orgreater riboflavin solution is applied every 30-60 seconds for 5-30minutes. During this time, periodic assessments using slit-lampmicroscopy are used to assess the concentration and homogeneity ofstromal saturation. Thereafter, a custom mask is applied to the surfaceof the cornea and/or sclera, thereby allowing for UVA or UVA and bluelight irradiation of selected areas of the cornea and/or sclera. A UVAor UVA/blue light of wavelength of from 365 -420 nm for deepercross-linking is used to deliver an irradiance of from 3 to 30 mW/cm2,in discontinuous cycles variable from 1 second to 1 minute or more, andthrough a reticule with an apertures that provides a specific lightdistribution pattern to cross-link selected areas of the cornea and/orsclera.

While only certain embodiments have been set forth, alternativeembodiments and various modifications will be apparent from the abovedescriptions to those skilled in the art. These and other alternativesare considered equivalents and within the spirit and scope of thisdisclosure. The above description of the disclosed embodiments isprovided to enable any person skilled in the art to make or use theinvention. Various modifications to these embodiments will be readilyapparent to those skilled in the art, and the generic principlesdescribed herein can be applied to other embodiments without departingfrom the spirit or scope of the invention. Thus, it is to be understoodthat the description and drawings presented herein represent a presentlypreferred embodiment of the invention and are therefore representativeof the subject matter which is broadly contemplated by the presentinvention. It is further understood that the scope of the presentinvention fully encompasses other embodiments that may become obvious tothose skilled in the art and that the scope of the present invention isaccordingly limited by nothing other than the appended claims.

What is claimed is:
 1. An ophthalmic treatment system, comprising: alight source device comprising at least one light source; at least oneoptical treatment head operatively coupled to the light source device,and configured to provide at least one treatment light; at least oneprocessor associated with the light source device and programmed tocontrol operation of the light source device to provide a discontinuoustreatment light projection onto a patient's eye for a selected treatmenttime comprising successive treatment light exposure periods of a firstlight intensity level separated by non-treatment periods at a secondlight intensity level lower than the first light intensity level; andwherein the at least one optical treatment head projects the treatmentlight at least two inches to the patient's eye such that a position ofthe at least one optical treatment head relative to the patient's eyeallows physician visualization and accessibility to the patient's eyeduring treatment.
 2. The ophthalmic treatment system of claim 1, whereinthe at least one optical treatment head projects the treatment light atleast three inches to the patient's eye.
 3. The ophthalmic treatmentsystem of claim 1, wherein the at least one optical treatment headprojects the treatment light between three to six inches to thepatient's eye.
 4. The ophthalmic treatment system of claim 1, whereinthe treatment light is selected from the group consisting of UVA light,blue light, and a mixture of UVA and blue light.
 5. The ophthalmictreatment system of claim 1, wherein the treatment light exposure periodis between one second and 10 minutes.
 6. The ophthalmic treatment systemof claim 1, wherein the at least one processor has an input for operatorselection of parameters and duration for the discontinuous lightprojection on the cornea and/or sclera.
 7. The ophthalmic treatmentsystem of claim 1, wherein each treatment light exposure period andnon-treatment period of the discontinuous treatment light projection isin the range from 5 seconds to 25 seconds.
 8. The ophthalmic treatmentsystem of claim 1, wherein the at least one processor further comprisesan intensity control module for gradually decreasing and increasing anintensity of the discontinuous treatment light projection between thefirst light intensity and the second light intensity.
 9. The ophthalmictreatment system of claim 1, further comprising a pattern control devicewhich provides patterned treatment light projection onto the eye. 10.The ophthalmic treatment system of claim 1, further comprising anoptical sensor device having an output in communication with the atleast one processor, wherein the at least one processor furthercomprises a treatment light control module which adjusts the intensityof part or all of the light source according to data collected from theoptical sensor device.
 11. The ophthalmic treatment system of claim 1,further comprising a fixation light upon which an eye is focused duringtreatment.
 12. The ophthalmic treatment system of claim 1, wherein theat least one optical treatment head is further configured to provide ananti-startle light of visible colored light from the light sourcedevice.
 13. The ophthalmic treatment system of claim 12, wherein the atleast one processor is further programmed to switch on the anti-startlelight to be directed towards the patient's eye.
 14. The ophthalmictreatment system of claim 1, wherein the second light intensity level is0%.
 15. The ophthalmic treatment system of claim 1, wherein the at leastone processor is programmed to control operation of a light modulationdevice of the light source device to provide the discontinuous treatmentlight projection onto the patient's eye.